In vivo three-dimensional kinematics of normal knees during different high-flexion activities.

AIMS: In Asia and the Middle-East, people often flex their knees deeply in order to perform activities of daily living. The purpose of this study was to investigate the 3D kinematics of normal knees during high-flexion activities. Our hypothesis was that the femorotibial rotation, varus-valgus angle, translations, and kinematic pathway of normal knees during high-flexion activities, varied according to activity. MATERIALS AND METHODS: We investigated the in vivo kinematics of eight normal knees in four male volunteers (mean age 41.8 years; 37 to 53) using 2D and 3D registration technique, and modelled the knees with a computer aided design program. Each subject squatted, kneeled, and sat cross-legged. We evaluated the femoral rotation and varus-valgus angle relative to the tibia and anteroposterior translation of the medial and lateral side, using the transepicodylar axis as our femoral reference relative to the perpendicular projection on to the tibial plateau. This method evaluates the femur medially from what has elsewhere been described as the extension facet centre, and differs from the method classically applied. RESULTS: During squatting and kneeling, the knees displayed femoral external rotation. When sitting cross-legged, femurs displayed internal rotation from 10° to 100°. From 100°, femoral external rotation was observed. No significant difference in varus-valgus angle was seen between squatting and kneeling, whereas a varus position was observed from 140° when sitting cross-legged. The measure kinematic pathway using our methodology found during squatting a medial pivoting pattern from 0° to 40° and bicondylar rollback from 40° to 150°. During kneeling, a medial pivot pattern was evident. When sitting cross-legged, a lateral pivot pattern was seen from 0° to 100°, and a medial pivot pattern beyond 100°. CONCLUSION: The kinematics of normal knees during high flexion are variable according to activity. Nevertheless, our study was limited to a small number of male patients using a different technique to report the kinematics than previous publications. Accordingly, caution should be observed in generalizing our findings. Cite this article: Bone Joint J 2018;100-B:50-5.

A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.

Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.

High-fidelity transmission acquired via a developmental decrease in NMDA receptor expression at an auditory synapse.

Central auditory relay synapses in mature animals follow high-frequency inputs for computation of sound localization. In immature mice, however, transmission at the calyx of Held synapse in auditory brainstem was inaccurate for high-frequency inputs because the summed slow synaptic potential components caused aberrant firings or blocked action potentials. As the mice matured, synaptic potentials became shorter, with smaller and faster NMDA receptor components, thereby establishing the precise one-to-one transmission for high-frequency inputs. Developmental acquisition of this high-fidelity transmission could be mimicked experimentally in immature mice by blocking NMDA receptors with d(-)2-amino-5-phosphonovaleric acid (d-APV). Furthermore, bilateral cochlear ablations at postnatal day 7 (P7) attenuated the developmental decrease of NMDA receptor expression and prevented the acquisition of high-fidelity transmission. We suggest that auditory activity, which begins at P10-P12 in mice, downregulates the expression of postsynaptic NMDA receptors, thereby contributing to the establishment of high-fidelity synaptic transmission.

Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon 1 or epsilon 2 subunit.

1. We have explored the effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor epsilon 1 or epsilon 2 subunit gene on NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) and long-term potentiations (LTPs) at the two types of synapse in mouse hippocampal CA3 pyramidal neurons: those formed by the commissural/associational (C/A) and fimbrial (Fim) inputs. 2. Electrophysiological experiments were performed in hippocampal slices prepared from both wild-type and epsilon 1- or epsilon 2-disrupted mice using extracellular and whole-cell patch recording techniques. To assess the epsilon 1, epsilon 2 and zeta 1 subunit expression at cellular levels, we performed non-isotopic in situ hybridization with digoxigenin-labelled cRNA probes. 3. We could record EPSCs in response to the stimulations to either of the C/A and Fim afferents from a single CA3 pyramidal neuron. The epsilon 1, epsilon 2 and zeta 1 subunits were expressed together in individual CA3 neurons. 4. The epsilon 1 subunit disruption selectively reduced NMDA EPSCs and LTP in the C/A-CA3 synapse without significantly affecting those in the Fim-CA3 synapse, whereas the epsilon 2 subunit mutation diminished NMDA EPSCs and LTP in the Fim-CA3 synapse with no appreciable functional modifications in the C/A-CA3 synapse. 5. These results suggest that NMDA receptors with different subunit compositions function within a single CA3 pyramidal cell in a synapse-selective manner.

Comparison of surface antigens on eosinophils from patients with eosinophilia.

Recent studies have suggested that there may be heterogeneity among human eosinophils. To study this further, surface antigens on blood eosinophils from patients with eosinophilia (23 bronchial asthma, 6 eosinophilic pneumonia, 1 Kimura's disease and 1 adult T-cell leukemia) and from 8 control subjects were examined using a new direct method for fluorescence detection of eosinophils. HLA-DR+ and CD4+ eosinophil counts were higher in patients with bronchial asthma and adult T-cell leukemia (ATL) than in patients from other groups and in control subjects. CD11b+ eosinophil counts in Kimura's disease and ATL were smaller than those in the other groups. CD45RO+ eosinophil counts in bronchial asthma and eosinophilic pneumonia were significantly higher (p < 0.05) compared with Kimura's disease, ATL and control subjects. CD44+ eosinophil counts in eosinophilic pneumonia were significantly higher (p < 0.05) compared with the other groups and control subjects. These results suggest the existence of functional heterogeneity in the different eosinophilic diseases, with eosinophils in bronchial asthma and eosinophilic pneumonia being more highly activated in migration, activation and immunoregulation. On the other hand, eosinophils in Kimura's disease and ATL might be functionally down-regulated. This heterogeneity of eosinophils may reflect differences in the pathogenesis of various eosinophilic diseases.

[An acute epidural hematoma soon after nose blowing: a case report].

We reported a very rare case of an epidural hematoma soon after nose blowing. A 22-year-old male visited our hospital complaining of severe headache and nausea soon after he blew his nose. Thirteen years ago, he had a ventriculo-peritoneal (V-P) shunt operation for a pineal region tumor which had not recurred after irradiation. His left auditory tube had been patent. He hit his head about 3 months ago. On his arrival, his consciousness was almost clear but we observed slight right hemiparesis. Computed tomography of his head obtained on the first day showed the air in the hematoma in the left parietal epidural space which penetrated his petrosal bone from the mastoid air cells. Removal of his epidural hematoma was performed the next day and there was no abnormality of his parietal bone, dura and meningeal arteries. We supposed that nose blowing was what triggered his epidural hematoma. From pressure of nose blowing, the air of his nasopharyngeal space passed through his patent auditory tube into the tympanic cavity, and entered into the epidural space penetrating a microfracture or dissociation in the petrosal bone. In addition to this, V-P shunt system and the looser adhesion of dura to the skull in the young promoted entrance of air. Associated with formation of epidural hematoma in this case were four factors, "patency of auditory tube", "defect or microfracture of petrosal bone", "V-P shunt", "younger age" and triggered by nose blowing.